Multidrug-resistant tuberculosis (MDR-TB) is caused by Mycobacterium tuberculosis strains that are resistant to the two most effective anti-TB drugs: isoniazid (INH) and rifampin (RIF). Despite efforts to prevent MDR- TB from occurring in California, there are still 40-50 cases per year. Over 80% of the MDR-TB cases are foreign-born and 25% of these cases are from Mexico. But it is not clear whether these cases entered the US already infected with MDR-TB or whether their MDR-TB was acquired from treatment failures of drug- sensitive TB within the US. Taking advantage of a CDC-funded program to genotype all California TB cases since 2004, and the first Mexican national MDR-TB survey-scheduled to be completed by the end of 2008-I propose to compare the genotypes and drug resistance mutations of MDR-TB cases from California, with genotypes and drug-resistance mutations of MDR-TB cases from Mexico. This analysis will allow us to determine if the MDR-TB pathogen population is developing independently on both sides of the border, or if drug resistant strains of TB are being transmitted binationally via migration.The hypothesis driving this proposal is that California MDR-TB strains in Hispanics are predominantly a subset of the Mexico MDR-TB strains, indicating binational transmission of primary drug resistance rather than independent acquisition of resistance on both sides of the border. In order to test this hypothesis, the following aims are proposed: Aim 1: To determine the extent to which MDR-TB pathogen strains in California are related to those in Mexico by comparing the genotypes of MDR-TB isolates from Hispanics in California, with MDR-TB genotypes from the Mexican National MDR-TB Survey. Aim 2: To determine whether INH and RIF drug resistance mutations in the matched MDR-TB isolates identified in Aim 1 resulted from direct transmission (same genotype, same drug mutations) or independent acquisition (same genotype, different drug mutation). Aim 3: To compare MDR-TB risk factors and mobility characteristics between MDR-TB cases from California and Mexico using a combination of retrospective analysis of reference laboratory data from Mexico and California, and from a prospective survey of MDR-TB cases in San Diego County, California and Tijuana, Mexico. RELEVANCE (See instructions): MDR-TB cases are exponentially more complicated and up to 20 times more expensive to treat than drug- sensitive TB, and case fatality ranges from 12% up to 90%. With only a limited TB control budget, it is critical to know how to focus MDR-TB prevention efforts. This study will identify the risk factors and transmission dynamics of cross-border MDR-TB in order to shape future public health interventions.